The major aim of this proposal is to provide evidence that hyaluronate is an important component in the regulation of morphogenetic sequences involved in the development of several tissues such as cartilage, cornea and brain. Our prevous work has led to a hypothesis that, during development, remodelling and repair, hyaluronate prevents certain interactions between mesenchymal cells which promote their differentiation, thus providing a facilitatory milieu for their migration and proliferation until the inhibitory effect of the hyaluronate is reversed and it is removed by hyaluronidase action. We propose to examine the interaction of hyaluronate with chondrogenic mesenchyme cells in vitro by measuring its binding to these cells and its effect on cyclic AMP levels, cell surface glycosyltransferase activities and extracellular events such as collagen assembly and proteoglycan-cell interaction. We will then examine the effect of thyroxine on the hyaluronate-cell interaction as measured above. In addition we will purify and prepare antibody to hyaluronidase in order to locate it and examine its function in the removal of hyaluronate at critical stages in the development of several tissues. By pursuing the above studies we are hoping to gain insight into disorders of development such as craniofacial anomalies arising from aberrant migration of neural crest cells.